title: Diffusion tensor imaging of the hippocampus and verbal memory performance: the RUN DMC study.
abstract: BACKGROUND
  Cerebral small vessel disease (SVD) and hippocampal atrophy are related to verbal memory failures and may ultimately result in Alzheimer's disease. However, verbal memory failures are often present before structural changes on conventional MRI appear. Changes in microstructural integrity of the hippocampus, which cannot be detected with conventional MRI, may be the underlying pathological substrate. With diffusion tensor imaging (DTI), we investigated the relation between the microstructural integrity of the hippocampus and verbal memory performance in 503 nondemented elderly with SVD.
  
  
  METHODS
  The Radboud University Nijmegen Diffusion tensor and Magnetic resonance imaging Cohort study is a prospective cohort study among 503 nondemented elderly with cerebral SVD aged between 50 and 85 years. All participants underwent T1 MPRAGE, fluid-attenuated inversion recovery, DTI scanning and the Rey Auditory Verbal Learning Test. After manual segmentation of the hippocampi, we calculated the mean diffusivity (MD) and fractional anisotropy in both hippocampi. The relation between memory performance and hippocampal DTI parameters was adjusted for age, sex, education, depressive symptoms, hippocampal, and white-matter lesions volume and lacunar infarcts.
  
  
  RESULTS
  We found inverse relations between hippocampal MD and verbal memory performance (β = -0.22; P < 0.001), immediate recall (β = -0.22; P < 0.001), delayed recall (β = -0.20; P < 0.001), and forgetting rate (β = -0.13; P = 0.025), most pronounced in participants with a normal hippocampal volume.
  
  
  CONCLUSIONS
  Microstructural integrity of the hippocampus assessed by DTI is related to verbal memory performance in elderly with SVD, also in participants with an intact appearing hippocampus. Changes in hippocampal microstructure may be an early marker of underlying neurodegenerative disease, before macrostructural (i.e., volumetric) changes occur.
authors.affiliation: Department of Neurology, Donders Institute for Brain, Cognition and Behaviour, Centre for Neuroscience, Radboud University Nijmegen Medical Centre, 6500 HB Nijmegen, The Netherlands.
authors.forename: Anouk G W
authors.initials: AG
authors.lastname: van Norden
authors.forename: Karlijn F
authors.initials: KF
authors.lastname: de Laat
authors.forename: Ilma
authors.initials: I
authors.lastname: Fick
authors.forename: Inge W M
authors.initials: IW
authors.lastname: van Uden
authors.forename: Lucas J B
authors.initials: LJ
authors.lastname: van Oudheusden
authors.forename: Rob A R
authors.initials: RA
authors.lastname: Gons
authors.forename: David G
authors.initials: DG
authors.lastname: Norris
authors.forename: Marcel P
authors.initials: MP
authors.lastname: Zwiers
authors.forename: Roy P C
authors.initials: RP
authors.lastname: Kessels
authors.forename: Frank-Erik
authors.initials: FE
authors.lastname: de Leeuw
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016880:Anisotropy; D059345:Cerebral Small Vessel Diseases / Q000150:complications / Q000473:pathology*; D015331:Cohort Studies; D038524:Diffusion Magnetic Resonance Imaging; D042241:Early Diagnosis; D005260:Female; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D008297:Male; D008568:Memory / Q000502:physiology; D008569:Memory Disorders / Q000209:etiology / Q000473:pathology*; D008875:Middle Aged